Crizotinib, a new drug developed by Pfizer to treat lung cancer, is one of the first targeted therapy in the treatment of anaplastic lymphoma kinase (ALK), active in ALK-positive locally advanced or metastaticnon-small cell lung cancer and it is described chemically as 3-(R)-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyridin-2-amine.

Currently, the commonly used methods for preparing crizotinib are, for example, as described in America patent application of Pfizer with publication no. US20060128724.
Method 1:

Many steps in the method were included and reagent was wasted for two Boc groups were introduced into the intermediate compound 5-bromo-3-(1-(6-dichloro-3-fluorophenyl) ethoxyl)-2-amino-pyridine which was then coupled with the borate, followed by the deprotection of the two Boc groups to produce 3-(1-(2,6-dichloro-3-fluorophenyl)ethoxyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-amino-pyridine. This product was subjected to Suzuki coupling reaction with 4-(4-bromo-1H-pyrazol-4-yl)pyridin-2-amine, followed by removal of the Boc group to finally generate crizotinib. The deprotection of Boc group being repeated twice results intedious steps. In addition, both the coupling products were purified on silica gel column chromatography, these led to longer reaction cycle and the limit of industrial production.
Method 2:

Sodium hydride is difficult to handle and may cause explosion easily in this method.
Method 3:

More byproducts were generated in this method, for the free amino group of 5-bromo-3-(2,6-dichloro-3-fluorophenyl)ethoxy)2-amino-pydine wasn't protected. The product was produced in a low yield of 61% after purification on silica gel column chromatography.